Frontiers in Psychiatry
February 6, 2023
Candace R. Lewis, Joseph Tafur, Sophie Spencer et al.
29 citations
Epigenetic changes in hypothalamic-pituitary-adrenal (HPA) axis genes may predict successful psychotherapy for post-traumatic stress disorder (PTSD). In a pilot sub-study of a Phase 3 clinical trial, 23 participants (16 receiving MDMA-assisted therapy, 7 receiving placebo with therapy) provided saliva samples. Methylation at 259 CpG sites across three HPA genes (CRHR1, FKBP5, NR3C1) was measured before and after treatment. Methylation changes across both groups significantly predicted symptom reduction on 37 of the sites, with two surviving false discovery rate correction. The MDMA group showed greater methylation change on one NR3C1 site compared to placebo. Therapy-related PTSD symptom improvements may be linked to DNA methylation changes in HPA genes, and such changes may be larger with MDMA-assisted therapy.
International Journal of Mental Health and Addiction
April 1, 2024
Christine Diindiisi Mccleave, Susan Beaulieu, Rainbow Lopez et al.
9 citations
Indigenous experts, students, and practitioners from North America discuss the historical context of colonialism within the Psychedelic Renaissance, the duality of Spirit and science, and the challenges Indigenous people face in psychedelic spaces. The commentary examines how culture aids healing trauma, the harms inflicted upon Indigenous Peoples, conflicting worldviews between Indigenous cultures and Western culture, and differences in scientific and economic paradigms. The authors analyze colonization's effects on relationships with one another and with entheogenic plant medicines.
bioRxiv Preprint Server
July 3, 2025
Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al.
1 citation
preprint
Psychedelic compounds like ketamine and MDMA induce widespread DNA methylation changes in brain-enriched genes, with ketamine altering 1,210 CpG sites and MDMA affecting 2,074 CpG sites. These changes occur in genes involved in neuroplasticity, immune regulation, and mental processes, with overlapping effects in genes such as PTPRN2 and SHANK2. The findings suggest shared epigenetic mechanisms through which psychedelics may drive increased neuroplasticity and produce lasting molecular changes relevant to neuroimmune function and psychiatric health.
Translational Psychiatry
July 11, 2026
Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al.
Ketamine and MDMA, compounds known as psychoplastogens, show therapeutic potential for mood and trauma-related disorders, but their molecular mechanisms are not fully understood. In a study analyzing blood samples from 20 ketamine-treated participants and saliva samples from 16 MDMA-treated participants, DNA methylation changes were examined using a Brain-Epigenome-Wide Association Study targeting brain-relevant genes. Ketamine was associated with 405 significantly altered genes and 169 functional networks, while MDMA was linked to 346 altered genes and 183 networks. Both compounds converged on pathways related to neuroplasticity and neuroimmune regulation, suggesting they induce peripheral epigenetic changes that engage molecular pathways relevant to psychiatric health.